Cyclic forms of the alpha-keto acid analogs of arginine, citrulline, homoarginine, and homocitrulline.

Abstract

The alpha-keto acid analogs of arginine and citrulline (and of their next higher homologs, homoarginine and homocitrulline) were prepared enzymatically and shown to exist in equilibrium with cyclic forms which predominate in solution and in the solid state. The cyclic forms of the alpha-keto acid analogs of arginine and homoarginine have the structures pyrrolidine-1-amidino-2-hydroxy-2-carboxylic acid and piperidine-1-amidino-2-hydroxy-2-carboxylic acid, respectively. The cyclic forms of the alpha-keto acid analogs of citrulline and homocitrulline have the structures pyrrolidine-1-carbamyl-2-hydroxy-2-carboxylic acid and piperidine-1-carbamyl-2-carboxylic acid, respectively. The latter compound can undergo further cyclization and dehydration to form additional products, whose structures (2H, 5H, 7H-imidazo[1,5-a]pyridine-1,3-dione and 2H, 5H, 7H, 9H-9-hydroxy-imidazo[1,5-a]pyridine-1,3-dione) were deduced. The alpha-keto acids investigated here, which may be formed reversibly by enzymatic transamination of the corresponding amino acids, may be formed in vivo especially in the presence of metabolic abnormalities associated with inborn enzymatic defects.